Hongnan Liu

Key mediators of intracellular amino acids signaling to mTORC1 activation.

Mammalian target of rapamycin complex 1 (mTORC1) is activated by amino acids to promote cell growth via protein synthesis. Specifically, Ras-related guanosine triphosphatases (Rag GTPases) are activated by amino acids, and then translocate mTORC1 to the surface of late endosomes and lysosomes. Ras homolog enriched in brain (Rheb) resides on this surface and directly activates mTORC1. Apart from the presence of intracellular amino acids, Rag GTPases and Rheb, other mediators involved in intracellular amino acid signaling to mTORC1 activation include human vacuolar sorting protein-34 (hVps34) and mitogen-activating protein kinase kinase kinase kinase-3 (MAP4K3). Those molecular links between mTORC1 and its mediators form a complicate signaling network that controls cellular growth, proliferation, and metabolism. Moreover, it is speculated that amino acid signaling to mTORC1 may start from the lysosomal lumen. In this review, we discussed the function of these mediators in mTORC1 pathway and how these mediators are regulated by amino acids in details.

Impact of the Gut Microbiota on Intestinal Immunity Mediated by Tryptophan Metabolism

The gut microbiota influences the health of the host, especially with regard to gut immune homeostasis and the intestinal immune response. In addition to serving as a nutrient enhancer, L-tryptophan (Trp) plays crucial roles in the balance between intestinal immune tolerance and gut microbiota maintenance. Recent discoveries have underscored that changes in the microbiota modulate the host immune system by modulating Trp metabolism. Moreover, Trp, endogenous Trp metabolites (kynurenines, serotonin, and melatonin), and bacterial Trp metabolites (indole, indolic acid, skatole, and tryptamine) have profound effects on gut microbial composition, microbial metabolism, the hosts immune system, the host-microbiome interface, and host immune system–intestinal microbiota interactions. The aryl hydrocarbon receptor (AhR) mediates the regulation of intestinal immunity by Trp metabolites (as ligands of AhR), which is beneficial for immune homeostasis. Among Trp metabolites, AhR ligands consist of endogenous metabolites, including kynurenine, kynurenic acid, xanthurenic acid, and cinnabarinic acid, and bacterial metabolites, including indole, indole propionic acid, indole acetic acid, skatole, and tryptamine. Additional factors, such as aging, stress, probiotics, and diseases (spondyloarthritis, irritable bowel syndrome, inflammatory bowel disease, colorectal cancer), which are associated with variability in Trp metabolism, can influence Trp–microbiome–immune system interactions in the gut and also play roles in regulating gut immunity. This review clarifies how the gut microbiota regulates Trp metabolism and identifies the underlying molecular mechanisms of these interactions. Increased mechanistic insight into how the microbiota modulates the intestinal immune system through Trp metabolism may allow for the identification of innovative microbiota-based diagnostics, as well as appropriate nutritional supplementation of Trp to prevent or alleviate intestinal inflammation. Moreover, this review provides new insight regarding the influence of the gut microbiota on Trp metabolism. Additional comprehensive analyses of targeted Trp metabolites (including endogenous and bacterial metabolites) are essential for experimental preciseness, as the influence of the gut microbiota cannot be neglected, and may explain contradictory results in the literature.

Effects of the Sequence of Isocaloric Meals with Different Protein Contents on Plasma Biochemical Indexes in Pigs.

Nutrient composition and pattern of food intake may play a significant role in weight gain. The aim of this study was to document the effects of a daily 3-meal pattern with isocaloric diets containing different dietary protein contents on growth performance and different plasma biochemical indexes including amino acid plasma concentration in castrated male pigs. Then, 21 DLY (Duroc×Landrace×Yorkshire) pigs aged 60 days were assigned randomly into 3 groups: a control group (crude protein, CP 18.1%), a group receiving high then basal and then low CP meals (High-Low group) and a group receiving low then basal and then high CP meal (Low-High group) for 40 days with pigs being feed-restricted. On day 40, after 12 h fasting, blood samples were obtained for analysis. The results showed that the insulin/glucagon ratio was lower in the High-Low group (P<0.05) when compared with the control group. Compared with the control group, the average daily gain of pigs from the High-Low group increased by 14.10% (P = 0.046). Compared with the control group, serum gamma-glutamyl transferase (GGT) decreased significantly (P<0.05) in both the High-Low and Low-High groups. Plasma concentrations of branched-chain amino acids (BCAA: valine, isoleucine and leucine) increased in the Low-High group (P<0.05) when compared with the control group; and plasma methionine and serine decreased in both the two experimental groups (P<0.05). Compared with the High-Low group, all the BCAA increased significantly (P<0.05) in the Low-High group. These findings suggest that the sequence and quantity of alimentary protein intake affect the insulin/glucagon ratio, as well as amino acid concentrations including BCAA, methionine and serine. It is proposed that meal pattern with pigs receiving high then basal and then low CP meals daily may help to improve the weight gain of pigs.

Effects of yeast products on the intestinal morphology, barrier function, cytokine expression, and antioxidant system of weaned piglets

The goal of this study was to evaluate the effects of a mixture of yeast culture, cell wall hydrolysates, and yeast extracts (collectively “yeast products,” YP) on the performance, intestinal physiology, and health of weaned piglets. A total of 90 piglets weaned at 21 d of age were blocked by body weight, sex, and litter and randomly assigned to one of three treatments for a 14-d feeding experiment, including (1) a basal diet (control), (2) 1.2 g/kg of YP, and (3) 20 mg/kg of colistin sulfate (CSE). No statistically significant differences were observed in average daily feed intake, average daily weight gain, or gain-to-feed ratio among CSE, YP, and control piglets. Increased prevalence of diarrhea was observed among piglets fed the YP diet, whereas diarrhea was less prevalent among those fed CSE. Duodenal and jejunal villus height and duodenal crypt depth were greater in the control group than they were in the YP or CSE groups. Intraepithelial lymphocytes (IEL) in the duodenal and jejunal villi were enhanced by YP, whereas IEL in the ileal villi were reduced in weaned piglets fed YP. Secretion of jejunal and ileal interleukin-10 (IL-10) was higher and intestinal and serum antioxidant indexes were affected by YP and CSE. In YP- and CSE-supplemented animals, serum D-lactate concentration and diamine oxidase (DAO) activity were both increased, and intestinal mRNA expressions of occludin and ZO-1 were reduced as compared to the control animals. In conclusion, YP supplementation in the diets of weaned piglets appears to increase the incidence of diarrhea and has adverse effects on intestinal morphology and barrier function.中文概要目 的验证添加酵母混合物(酵母培养物、酵母细胞壁水解物和酵母提取物)对断奶仔猪生长性能、腹泻发生率、肠道形态、屏障功能、免疫反应和抗氧化系统的影响。创新点考察酵母培养物、酵母细胞壁水解物和酵母提取物混合物对断奶仔猪的协同作用。方 法90 头21 日龄断奶仔猪随机分为3 组,分别饲喂基础日粮(对照组),含1.2 g/kg 的酵母混合物(YP 组)及含20 mg/kg 硫酸粘杆菌素日粮(CSE组)14 天,比较三组间各项指标差异。结 论结果表明,三组之间平均日采食量、平均日增重和料肉比无显著差异。YP 组腹泻发生率显著高于其它两组。对照组十二指肠和空肠的绒毛高度以及十二指肠的隐窝深度显著高于YP 组和CSE组。相对于对照组或CSE 组, YP 组十二指肠和空肠绒毛淋巴细胞数目显著增加,而回肠绒毛内淋巴细胞数目显著降低。相对于对照组, YP 组空肠和回肠内白介素-10(IL-10)的分泌增加, YP 和CSE 也显著影响了仔猪肠道和血清中抗氧化因子;YP 和CSE 组血清D-乳酸浓度和二胺氧化酶活性都增强;YP 组或CSE 组肠道occludin和ZO-1 mRNA 表达降低。综上所述,酵母混合物添加会增加断奶仔猪腹泻发生率,并对断奶仔猪肠道形态学和屏障功能具有副作用。

Effects of dietary coated cysteamine hydrochloride on pork color in finishing pigs

BACKGROUND Coated cysteamine hydrochloride (CC) was applied as a feed additive in animal production. The influence and the mechanisms of CC used as a feed additive in promoting meat quality in finishing pigs were investigated. RESULTS Dietary CC supplementation increased (P < 0.05) the a* and H* values and reduced (P < 0.05) the L* value in the longissimus dorsi muscles at 48 h postmortem (P < 0.05). The deoxymyoglobin content was enhanced (P < 0.05) and the metmyoglobin and malondialdehyde contents were reduced (P < 0.05) in pigs fed the dietary CC. Pigs fed a dietary CC of 0.035 g kg-1 had a lower cooking loss (P < 0.05) and a higher a* (24 h) value in the longissimus dorsi muscles than pigs on control treatment. The messenger RNA expression of superoxide dismutase 1 was upregulated (P < 0.05) in the longissimus dorsi. CONCLUSION Dietary supplementation with CC could improve antioxidant status and delay meat discoloration by improving glutathione levels and antioxidase activity after longer chill storage (for 48 h after slaughter). Dietary supplementation with CC at 0.035 g kg-1 may promote the stability of pork color by reducing oxidation.

Redox Properties of Tryptophan Metabolism and the Concept of Tryptophan Use in Pregnancy

During pregnancy, tryptophan (Trp) is required for several purposes, and Trp metabolism varies over time in the mother and fetus. Increased oxidative stress (OS) with high metabolic, energy and oxygen demands during normal pregnancy or in pregnancy-associated disorders has been reported. Taking the antioxidant properties of Trp and its metabolites into consideration, we made four hypotheses. First, the use of Trp and its metabolites is optional based on their antioxidant properties during pregnancy. Second, dynamic Trp metabolism is an accommodation mechanism in response to OS. Third, regulation of Trp metabolism could be used to control/attenuate OS according to variations in Trp metabolism during pregnancy. Fourth, OS-mediated injury could be alleviated by regulation of Trp metabolism in pregnancy-associated disorders. Future studies in normal/abnormal pregnancies and in associated disorders should include measurements of free Trp, total Trp, Trp metabolites, and activities of Trp-degrading enzymes in plasma. Abnormal pregnancies and some associated disorders may be associated with disordered Trp metabolism related to OS. Mounting evidence suggests that the investigation of the use of Trp and its metabolites in pregnancy will be meanful.

Effects of dietary lysozyme levels on growth performance, intestinal morphology, immunity response and microbiota community of growing pigs: Effects of dietary lysozyme levels on growth performance, intestinal morphology, immunity response and microbiota community of growing pigs

BACKGROUND Lysozyme has been studied as a potential alternative to antibiotics for animals in recent years. The aim of this study was to evaluate the effect of dietary lysozyme on growth performance, serum biochemical parameters, immune response and gut health of growing pigs. RESULTS A total of 216 growing pigs (19.81 ± 0.47 kg) were fed the diets supplemented with colistin sulfate at 20 mg kg-1 (control), or lysozyme at 50 (L50) or 100 mg kg-1 (L100) diet for 30 days. The results showed that pigs fed with L100 or control had greater average daily gain and gain-to-feed ratio than pigs in the L50 group. Pigs fed with L100 or colistin had greater villus height to crypt depth ratio in jejunum compared with pigs in the L50 group. Pigs fed with L100 had greater serum immunoglobulin A and jejunal secretory immunoglobulin A than control and L50, but lower serum total protein and globulin than control. No differences were observed in the messenger RNA expression of genes related to mucosal cytokines, antioxidant capacity, enzyme activity, and barrier functions among three treatments. The caecal microflora evenness was lower in the L100 group than in the control or L50 group by 16S ribosomal DNA sequencing. Phylogenetic investigation of communities by reconstruction of unobserved states analysis predicted that lysozyme may modify nutrient metabolism by changing intestinal microbial function of pigs. CONCLUSIONS Pigs supplemented with 100 mg kg-1 lysozyme had similar growth performance and intestinal morphology as pigs fed with colistin. This was likely due to the improved systemic and gut immune responses and the reduced microbiota diversity by feeding 100 mg kg-1 lysozyme.